A functional adrenal cortex is essential for life as evidenced by the early death of patients with congenital adrenal hypoplasia. The autosomal recessive mouse mutant adrenocortical dysplasia (acd) is a good model for the study of adrenal organogenesis and shares some striking similarities with miniature adult congenital adrenal hypoplasia in humans. Similar to human patients, mutant acd/acd animals lack an "adrenocortical X zone and possess a dysfunctional definitive zone, and the majority die shortly after birth. Serum corticosterone levels are low and ACTH levels are significantly elevated, consistent with a primary adrenal defect. The identification and characterization of the acd mutation via the following specific aims is the focus of this proposal: Aim 1. Perform a detailed characterization of acd mutant animals; Aim 2. Refinement of the genetic and physical map of the acd locus on mouse chromosome 8, and Aim 3. Clone and characterize the acd gene. The identification of the acd gene will be an important step in the understanding of both normal and abnormal adrenal growth. These studies will provide the groundwork for future investigations of abnormal adrenal development in humans and may lead to important therapeutic applications for humans with congenital adrenal insufficiency. The career development program outlined in this proposal will build on my prior research experience and will also provide for the development of new techniques, interaction with a new mentor, and additional didactic training in Developmental Biology and Bioinformatics. The educational climate at the University of Michigan is outstanding and will allow me to foster these new skills. Ultimately, through this additional training I will be poised to continue my long-term career goal of becoming an Independent Investigator.